Validation of a Multivariate Serum Profile for Epithelial Ovarian Cancer Using a Prospective Multi-Site Collection

In previous studies we described the use of a retrospective collection of ovarian cancer and benign disease samples, in combination with a large set of multiplexed immunoassays and a multivariate pattern recognition algorithm, to develop an 11-biomarker classification profile that is predictive for the presence of epithelial ovarian cancer. In this study, customized, Luminex-based multiplexed immunoassay kits were GMP-manufactured and the classification profile was refined from 11 to 8 biomarkers (CA-125, epidermal growth factor receptor, CA 19-9, C-reactive protein, tenascin C, apolipoprotein AI, apolipoprotein CIII, and myoglobin). The customized kits and the 8-biomarker profile were then validated in a double-blinded manner using prospective samples collected from women scheduled for surgery, with a gynecologic oncologist, for suspicion of having ovarian cancer. The performance observed in model development held in validation, demonstrating 81.1% sensitivity (95% CI 72.6 – 87.9%) for invasive epithelial ovarian cancer and 85.4% specificity (95% CI 81.1 – 88.9%) for benign ovarian conditions. The specificity for normal healthy women was 95.6% (95% CI 83.6 – 99.2%). These results have encouraged us to undertake a second validation study arm, currently in progress, to examine the performance of the 8-biomarker profile on the population of women not under the surgical care of a gynecologic oncologist

Adjusting for treatment switching in the METRIC study shows further improved overall survival with trametinib compared with chemotherapy

Trametinib, a selective inhibitor of mitogen-activated protein kinase kinase 1 (MEK1) and MEK2, significantly improves progression-free survival compared with chemotherapy in patients with BRAF V600E/K mutation–positive advanced or metastatic melanoma (MM). However, the pivotal clinical trial permitted randomized chemotherapy control group patients to switch to trametinib after disease progression, which confounded estimates of the overall survival (OS) advantage of trametinib. Our purpose was to estimate the switching-adjusted treatment effect of trametinib for OS and assess the suitability of each adjustment method in the primary efficacy population. Of the patients randomized to chemotherapy, 67.4% switched to trametinib. We applied the rank-preserving structural failure time model, inverse probability of censoring weights, and a two-stage accelerated failure time model to obtain estimates of the relative treatment effect adjusted for switching. The intent-to-treat (ITT) analysis estimated a 28% reduction in the hazard of death with trametinib treatment (hazard ratio [HR], 0.72; 95% CI, 0.52–0.98) for patients in the primary efficacy population (data cut May 20, 2013). Adjustment analyses deemed plausible provided OS HR point estimates ranging from 0.48 to 0.53. Similar reductions in the HR were estimated for the first-line metastatic subgroup. Treatment with trametinib, compared with chemotherapy, significantly reduced the risk of death and risk of disease progression in patients with BRAF V600E/K mutation–positive advanced melanoma or MM. Adjusting for switching resulted in lower HRs than those obtained from standard ITT analyses. However, CI are wide and results are sensitive to the assumptions associated with each adjustment method

Functional and symptom impact of trametinib versus chemotherapy in BRAF V600E advanced or metastatic melanoma: quality-of-life analyses of the METRIC study

We report the first quality-of-life assessment of a MEK inhibitor in metastatic melanoma from a phase III study. Trametinib prolonged progression-free survival and improved overall survival versus chemotherapy in patients with BRAF V600 mutation-positive melanoma. Less functional impairment, smaller declines in health status, and less exacerbation of symptoms were observed with trametini

Trichobezoars as a cause of intestinal obstruction in a young female

A bezoar is a mass found trapped in the gastrointestinal system, though it can occur in other locations. There are various types of bezoars including food boluses, lactobezoar, pharmacobezoar, phytobezoar, diospyrobezoar and trichobezoar. They are common in children and adolescents, and 90% of the patients are women. Complications may manifest as gastric outlet obstruction or bleeding and intestinal obstruction. CT is the preferred image modality for the evaluation of suspected trichobezoars in order to characterize the size, location, presence and level of obstruction and complications such as ischemia or perforation. Here authors present a case to stress the importance of considering trichobezoars as one of the causes for intestinal obstruction in young females.

Performance Evaluation of Mutual Funds Using Risk Return Relationship Models - An Empirical Study

Purpose: The main purpose of this study is to analyse the performance of mutual funds using Risk- Return Relationship Models.   Theoretical framework: One of India's most important financial intermediaries, mutual funds can provide a wide range of financial services to small and large investors. They are also involved in the country's transformation, and their market participation has become more important. Evaluating a mutual fund's performance concerns investors, researchers, and fund managers. It should be conducted in a way that helps investors make informed decisions and maximize returns. A regular evaluation of a fund's performance is also essential for investors.   Design/methodology/approach: The performance of 12 growth-oriented mutual funds has been evaluated using three Risk Adjusted performance measures, namely the Treynor index, Sharpe index, and Jensen measure. Treynor Index, developed by Treynor and Mazuy (1966), defined the measure as the ratio of returns to systematic Risk (Beta). The higher the ratio better the performance. Sharpe Index, developed by Sharpe (1964) defined as the ratio of returns to the variability of returns. Jensen's measure (Jensen 1968) regresses excess fund return with the excess market return. Monthly data was used during the period from Jan 2015 to Dec 2019. Further monthly returns of 12 diversified Equity mutual funds were compared with the returns of the B.S.E.( Bombay Stock Exchange) national index during the same period.   Findings:  It is identified from the results that the mutual funds have not performed better than their benchmark indicators except the ICICI Multi-asset fund and HDFC mid-cap opportunity fund in terms of a non-risk adjusted measure of the average returns as well as in terms of Risk-adjusted performance measures.   Research, Practical & Social implications: Fund houses, Fund managers, researchers, and mutual fund investors can benefit more from a strong risk management foundation. It can help them make informed decisions and maximize their returns.   Originality/value: This study differs from past studies because it examined the risk-adjusted performance of a few mutual funds, which ultimately may use by investors and policymakers to enhance the returns in these funds

Intrapartum vulvovaginal haematoma causing obstructed labour: an obstetricians nightmare

Vulval hematoma during pregnancy is a rare event. Typically, they arise as a result of postpartum trauma. Rarely do hematomas of this type develop spontaneously during labour without any obvious underlying cause for the same. Prompt recognition and timely drainage of the hematoma helps to prevent any untoward complication and leads to speedy recovery

Potential climate predictability of renewable energy supply and demand for Texas given the ENSO hidden state

Climate variability influences renewable electricity supply and demand and hence system reliability. Using the hidden states of the sea surface temperature of tropical Pacific Ocean that reflect El Niño-Southern Oscillation (ENSO) dynamics that is objectively identified by a nonhomogeneous hidden Markov model, we provide a first example of the potential predictability of monthly wind and solar energy and heating and cooling energy demand for 1 to 6 months ahead for Texas, United States, a region that has a high penetration of renewable electricity and is susceptible to disruption by climate-driven supply-demand imbalances. We find a statistically significant potential for oversupply or undersupply of energy and anomalous heating/cooling demand depending on the ENSO state and the calendar month. Implications for financial securitization and the potential application of forecasts are discussed

Factors related to longitudinal adherence in colorectal cancer screening:qualitative research findings

Background: The effectiveness of screening in colorectal cancer prevention depends on sustained participation rates. The objective of this study was to explore factors related to the longitudinal adherence of screening behavior in the context of a biennial population-based cancer screening program. Methods: Eight focus groups were conducted with individuals who were invited two or three consecutive times to a population-based colorectal cancer screening program using a fecal occult blood test and who agreed to participate in the program at least once (n = 45). The criteria used to select the study members included adherence to fecal occult blood test maintenance, factors regarding their initial participation in the colorectal cancer screening, sex, and contextual educational level. Results: The participants expressed a high level of satisfaction with the program; however, they showed a low level of understanding with respect to cancer screening. Consulting a general practitioner was cited by all participants as an important factor that mediated their final decision or influenced their behavior as a whole with regard to the program. Fear played a different role in the screening behavior for regular and irregular adherent participants. In the adherent participants, fear facilitated their continued participation in the screening program, whereas for the irregular participants, fear led them to avoid or refuse further screening. Having a close person diagnosed with colorectal cancer was a facilitator for the regular adherent participants. The irregular adherent participants showed some relaxation with respect to screening after a negative result and considered that further screening was no longer necessary. Conclusion: Considering the importance of primary healthcare professionals in the decision regarding sustained participation, it is important to better engage them with cancer screening programs, as well as improve the communication channels to provide accurate and balanced information for both health professionals and individuals.</p

Fetal Tracheal Occlusion Correlates with Normalized YAP Expression and Alveolar Epithelial Differentiation in Congenital Diaphragmatic Hernia

Alveolar epithelial differentiation; Congenital diaphragmatic hernia; Fetal tracheal occlusionDiferenciació epitelial alveolar; Hèrnia diafragmàtica congènita; Oclusió traqueal fetalDiferenciación epitelial alveolar; Hernia diafragmática congénita; Oclusión traqueal fetalCongenital diaphragmatic hernia (CDH) is characterized by incomplete closure of the diaphragm. Although the ensuing compression to the fetal lung causes lung hypoplasia, specific cellular phenotypes and developmental signaling defects in the alveolar epithelium in CDH are not fully understood. Employing lung samples from human CDH, a surgical lamb model, and a nitrofen rat model, we investigated whether lung compression impairs alveolar epithelial differentiation and Yes-associated protein (YAP)-mediated mechanosensing. We showed that CDH in humans and lambs caused defective alveolar epithelial differentiation manifested by more alveolar epithelial type II (ATII) cells, fewer ATI cells, and the emergence of cells coexpressing ATI and ATII markers. Associated with these alveolar epithelial defects, we found a decrease in the level and nuclear localization of YAP. Reduced YAP and abnormal distal lung development were evident as early as 21 weeks of gestation in human CDH. In addition, rat fetuses with CDH also showed diminished nuclear YAP and more abundant ATII cells. In contrast, the littermates without the hernia had no such alveolar phenotypes. Furthermore, fetal tracheal occlusion in the surgical lamb model of CDH fully normalized nuclear YAP and rescued alveolar epithelial defects in a gestational age-dependent manner. Taken together, our findings across species indicate that lung compression in CDH is sufficient to disrupt alveolar epithelial differentiation and impair YAP signaling. Tracheal occlusion can restore nuclear YAP and rescue the alveolar defects in CDH, depending on the timing and the duration of this prenatal surgical intervention

Design Thinking and Methods in Library Practice and Graduate Library Education

Despite interest in the application of design thinking and methods in librarianship, there seems to be a disconnect between application and education to support it. This study used an online questionnaire to elicit feedback from library workers in the United States about interest in and use of design thinking and methods in library practice, and the need for design skills and abilities in library education. We found that practicing librarians perceive the relevance of design thinking and methods to library work, although opinions vary based on library and work type. Design thinking and methods were used mostly for space planning and program development, with applications disproportionally emphasizing empathy over other aspects such as prototyping and refinement. Additionally, library workers struggled with applying design concepts to intangible services and experiences. Increased education about design via MLIS programs, professional development opportunities, and/or repositories of example projects may help overcome some of the simplified and superficial applications of design thinking reported in this work